Project summary With better knowledge about the 3D structural organization of the genome comes the challenge of elucidating which factors determine these structures, what is their functional implications, and how are these structures modulated during cell processes such as cell differentiation or disease progression. Proteins and their complexes play critical roles in orchestrating chromatin interactions and chromosome folding. It is therefore important to link the discovery of endogenous protein complexes with their roles in the formation of specific chromatin interactions. Our goal in this component is to develop a new technology for elucidating the role of protein complexes in chromatin folding. Specifically we combine DNA-DNA proximity mapping with the discovery of the underlying causal protein complexes. We will develop the ?Genome Conformation Capture-Proteome? method (GCCP) for simultaneous detection of chromatin interactions and associated endogenous protein complexes. We will employ a proven pipeline for the isolation of native protein complexes, but extensively optimized for the purpose of reading out the chromatin interactome surrounding the detected specific protein complexes.